tbuckley/cabot-search huggingface dataset:
PB2077: COMPARISON OF PLASMA CELL PERCENTAGE BY BONE MARROW ASPIRATE MORPHOLOGY AND CD138-STAINED BONE MARROW BIOPSY IN SMOLDERING MYELOMA TO PREDICT TRANSFORMATION TO SYMPTOMATIC MYELOMA
Authors: Helen Cashman, Gurdeep Parmar
Journal: HemaSphere (2023)

Topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research Background: Smoldering myeloma (SM) can progress to symptomatic plasma cell myeloma (PCM) and usually requires a bone marrow (BM) plasma cell percentage (PC%) over 10% for diagnosis. PC quantification on BM examination includes PC% from the bone marrow aspirate (BMA) or the percentage of positive PCs on a CD138-stained bone marrow biopsy (BMB) specimen. It is not known which method of plasma cell enumeration at diagnosis correlates best with risk of progression of SM to PCM. Aims: We aimed to assess the BM PC% based on review of BMA and CD138-stained BMB in SM patients to determine if one method is more predictive of progression to PCM. Methods: Bone marrow examination records over a ten year period of patients diagnosed with smoldering myeloma were retrospectively reviewed. PC% based on BMA and BMB was determined and patients classified into Group 1 [both BMA and BMB PC%>10%] or Group 2 [BMA PC%<10% and BMB PC%>10%]. Patient records were reviewed to determine if patients progressed to PCM. Exclusion criteria included cases where the aspirate was aparticulate or the trephine biopsy sample inadequate or of poor quality. Results: 78 SM patients were included in the analysis. 23 patients had a PC% on both BMA examination and BMB of >=10% (Group 1). 55 patients had a PC% of 10% or greater on CD138-stained BMB but <10% on BMA examination (Group 2). No patients had PCs 10% or over on the aspirate smear alone. 24% of patients (19/78) progressed to PCM during the follow up period. 52% of patients in Group 1 transformed to PCM (12/23) compared to 13% patients in Group 2 (7/55 patients). Rate of progression was 20.5 and 3.9 per 100 person-years in Group 1 and Group 2 respectively. Median time to progression was 26 months in Group 1 and 31 months in Group 2. Median transformation-free survival (TFS) was shorter in Group 1; 45 months in Group 1 and not reached in Group 2 (p<0.0003). Median follow up was 25 months in Group 1 (range 5 – 96) and 29 months in Group 2 (range 4 – 96) Summary/Conclusion: Our findings suggest that BMA-PC% is more predictive of transformation to PCM than BMB-PC% in SM patients. BMB morphological assessment retains significance where BMA sample quality is insufficient for analysis.Figure: Keywords: Plasma cells, Bone marrow biopsy, Multiple myeloma, Myeloma
PB1782: INTEGRATIVE MOLECULAR SUBTYPES OF ACUTE MYELOID LEUKEMIA
Authors: Qianxing Mo, Seongseok Yun, David Sallman, Nicole Vincelette, Guang Peng, Ling Zhang, Jeffrey Lancet, Eric Padron
Journal: HemaSphere (2023)

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: Molecular classification of Acute Myeloid Leukemia (AML) is of clinical significance for prognosis and target therapy. Currently, diagnosis and management of AML are heavily dependent on genetics-based risk classification, which does not capture the full complexity of the disease. In recent years, genomic, epigenomic and transcriptomic profiles have been used to define AML molecular subtypes. However, the multi-omics profiles have not been systematically combined to define integrative subtypes (iSubtypes) of AML, which could provide valuable information for understanding the underlying mechanisms of the disease. Aims: This study aimed to identify iSubtypes of AML and explore the subtype-specific multi-omics signatures that could be used for prognosis and targeted therapy in AML. Methods: We performed an integrative clustering (iCluster) analysis of the AML multi-omics data generated by The Cancer Genome Atlas (TCGA), which consisted of somatic mutation, DNA copy number, DNA methylation and gene expression data for 160 AML samples. We identified the multi-omics signatures that drove the molecular classification of AML. Based on the subtype-driver methylation and gene expression signatures, we derived a gene panel for classification of AML and validated the prognostic power of the gene panel using three independent AML datasets (n=1382). In addition, we compared our integrative classification with the genetics-based classification including ELN2022 and cytogenetics. Results: We identified 4 iSubtypes with distinct multi-omics signatures and prognoses. Specifically, we identified an iSubtype of normal-karyotype AML (NK-AML) that was characterized by high-frequency mutation of FLT3/NPM1/DNMT3A and high expression of genes involved in negative regulation of immune system process, which had an overall survival as worse as the iSubtype of complex-karyotypes AML (CK-AML) enriched with TP53 mutation. In addition, we identified an iSubtype of CK-AML deficient with TP53 mutation, which had a better overall survival than the iSubtype of CK-AML enriched with TP53 mutation. In terms of prognosis, the iSubtypes were comparable to the risk groups of ELN2022 and cytogenetics. Based on the common subtype-driver methylation and transcription signatures, we derived a 571-gene panel for classification of AML when transcriptomic data are available. Using three independent transcriptomic datasets (n=1,382), we demonstrated the prognostic power of the 571-gene panel in classification of AML into clinically relevant subtypes. Summary/Conclusion: By integrative analysis of multi-omics data, the study provides insights into the molecular heterogeneity of AML. The identification of iSubtypes and subtype-specific multi-omics signatures may aid in the development of more precise and personalized treatment approaches for patients with AML.Keywords: Acute myeloid leukemia
PB2016: HIGH SERUM FERRITIN LEVELS AT DIAGNOSIS PREDICT WORSE PROGNOSIS IN ADVANCED MDS IN CHILDREN.
Authors: Chenmeng Liu, Wenyu Yang
Journal: HemaSphere (2023)

Topic: 10. Myelodysplastic syndromes - Clinical Background: Childhood MDS is a clonal haematopoietic stem cell neoplasm arising in children and adolescents (<18 years of age) leading to ineffective haematopoiesis, cytopenia(s), and risk of progression to AML,with 10-25% presenting with increased blasts. Aims: In this study we aimed to explore the factors affecting the prognosis of advanced MDS in children. Methods: We reviewed 66 (47 males and 19 females) advanced pediatric MDS, including refractory anaemia with excess of blasts (RAEB; n =53) and RAEB in transformation (RAEB-T; n = 13), from September 2009 to June 2022 at our single center. Results: The median age at diagnosis was 8 (1-17) years.The 3-year probability of overall survival(OS) for children given allogeneic hematopoietic stem cell transplantation (HSCT) (n=39) or not (n=27) was 78.4% and 40.7%, respectively (p =0.001),with median observation time being 23(1-158) months. With patients not given HSCT,we divided the cohort into low (n = 6) and high (n =18) ferritin groups using a cutoff of 303.4 ng/mL.Kaplan–Meier analyses revealed that the 1-year overall survival (OS) of the high ferritin group was significantly shorter than that of the low ferritin group (41.7% and 71.8%, p =0.022) Summary/Conclusion: HSCT can significantly improve the prognosis of advanced pediatric MDS. Higher SF levels are associated with worse outcomes in advanced pediatric MDS.Keywords: MDS, Hematopoietic stem cell replication, Children, Ferritin
PB1997: TRISOMY 18 IN MYELODYSPLASTIC SYNDROMES
Authors: Nouha Bouayed Abdelmoula, Balkiss Abdelmoula, Sonda Kammoun, Samir Aloulou
Journal: HemaSphere (2023)

Topic: 9. Myelodysplastic syndromes - Biology & Translational Research Background: Myelodysplastic Syndromes (MDS) are highly heterogeneous clonal hematopoietic stem cell disorders. MSD are characterized by multilineage dysplasia, peripheral blood cytopenia, and a high risk of transformation to acute myeloid leukemia. Karyotyping is a major prognostic criteria in MDS. Cytogenetic abnormalities are described in about 50% of de novo MDS and much more in secondary MDS. While chromosomes 5 and 7 are the usual chromosomes involved in karyotyping abnormalities of MDS, many other rare cytogenetic abnormalities are reported in association with MDS. Aims: Our aim was to report MDS cases with trisomy 18 and to discuss the genetic basis of this chromosomal abnormality in MDS pathogenesis. Methods: Blood and marrow samples were studied from a cohort of 12 Tunisian patients presenting with MDS. Conventional karyotyping was performed according to standard procedures. Results: Cytogenetic abnormalities involving chromosome 18 in tested MDS Tunisian patients (n=12) were detected in two cases. The first case was a female patient (P1) with refractory anemia (RA) in progress for 54 months. The second case was a male patient (P2) with RA and excess blasts-T (RAEB-T) in transformation to acute myeloid leukemia. In P1, cytogenetic studies revealed the presence of a minor normal population associated to two different clones of blast cells harboring trisomy 18: 46,XX [5]/47,XX,+18 [19]/48,XX,+6,+18 [6]. The P2 had a del (5) (q21 q31) associated to a hyperploid clone with trisomy 18 and other chromosomal abnormalities: 51,XY,+X, +3,+der(4),del(5),+10,+18[30]. Summary/Conclusion: The mechanistic basis of MDS remain largely unknown, despite the identification of recurrent cytogenetic abnormalities as well as the discovery of various gene mutations mediating MDS pathogenesis and progression. Isolated trisomy 18 (as well as the cases of other various chromosomal aberrations) is very rare and uncommon in MDS. Three genes located at chromosome 18 may be involved in the pathogenesis of MDS associated to trisomy 18: BCL2, SETBP1 and SMAD4. In fact, BCL2 acting as a major negative regulator on apoptosis, plays a key role in leukemogenesis, and its overexpression contributes to MDS by blocking cell death. SMAD4 is a typical tumor suppressor in the TGF-β signaling pathway, and the loss of its integrity or expression has been documented in patients with myeloid malignancies. SETBP1 is suggested to inhibit various tumor suppressor effects and consequently promote cell proliferation. In MDS, SETBP1 mutations have been identified with an incidence of 3%-9%. Abnormal and additional chromosomes may have consequences for disease outcome due to changes in gene expression. Thus, we empathize the role of these genes and their potential mutations in MDS pathogenesis and progression. Keywords: Myelodysplastic syndrome, Chromosomal abnormality
PB2337: SHORT-TERM EFFICACY AND SAFETY OF ZANUBRUTINIB COMBINED WITH POMALIDOMIDE IN THE TREATMENT OF CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Zhipeng Zhang, Wen LI, Wenzhong Wu, Hong Liu, LI Yang, Kai Lu, Haijuan Ren, Zenghua Lin
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Central lymphoma includes two types, primary and secondary. Current treatment regiments are not effective in many patients. zanubrutinib is a BTK inhibitor and pomalidomide is an immunomodulator, which have been reported to be used in the treatment of central nervous system lymphoma. Aims: To investigate the efficacy and safety of zanubrutinib combined with pomalidomide in the treatment of primary or secondary central nervous system lymphoma. Methods: A total of 8 patients diagnosed with primary or secondary central nervous system lymphoma from October 2021 to January 2023 were included. They received zanubrutinib combined with pomalidomide based regimen for at least 2 courses, and the short-term efficacy and safety were analyzed. Results: Among the 8 patients, 7 were effective after 2 courses of treatment, 1 was lost to follow-up. 7 remained effective after 4 courses of treatment,2 patients had central recurrence after 5 courses of treatment, all of which were secondary central nervous system lymphoma involving cerebrospinal fluid, and 1 patient died of coronavirus disease (COVID-19） infection. The adverse reactions were mainly hemocytopenia and pulmonary infection. One case of hypokalemia was aggravated. The adverse events were controllable and improved after symptomatic treatment. Summary/Conclusion: The regimen based on zanubrutinib and pomalidomide has certain efficacy in the treatment of primary or secondary central nervous system lymphoma, and the combination of zanubrutinib and pomalidomide can further improve the response rate and remission time. However, due to the limited cases, the strength of relevant clinical suggestions needs to be further confirmed by expanding the sample size and multi-center studies. Keywords: Immunomodulation, Lymphoma therapy, Bruton’s tyrosine kinase inhibitor (BTKi)
PB1868: COMPARISON OF MYELOBLAST CELL PERCENTAGE IN INVESTIGATIONS FOR ACUTE MYELOID LEUKAEMIA INCLUDING FLOW CYTOMETRY, BONE MARROW ASPIRATION AND BONE MARROW TREPHINE
Authors: Naml Iftikhar
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Immunophenotyping with flow cytometry, bone marrow aspiration and bone marrow trephine are the main tests to measure the percentage of myeloblast cells in order to diagnose acute myeloid leukaemia (AML) and guide its treatment plan. AML is diagnosed when the myeloblast cell percentage is >20%. A successful bone marrow transplant can only be received if patient is in remission (myeloblast<5%) after chemotherapy. Aims: This study aims to compare the discrepancies of the myeloblast cell percentage for AML between these 3 tests to assess whether treatment has been guided correctly or if any intervention is required. Methods: Patients investigated for AML by flow cytometry, bone marrow aspiration and bone marrow trephine were assessed for inclusion if they had more than 1 test performed on the same day. 122 data sets from patients were suitable for the inclusion criteria. Myeloblast percentage was obtained from flow cytometry (n=122), bone marrow aspiration (n=119) and bone marrow trephine (n=24) in total. Data collected included the myeloblast cell percentage which was obtained by the database of the institution. Data was correlated on Microsoft excel and analysed using the two tailed T-test. The correlation coefficient (R) was used to measure the strength of the linear relationships between 2 variables. Results: Results obtained from flow cytometry and bone marrow aspiration results had a mean difference of 2% (R=0.972, P=0.011). Flow cytometry and bone marrow trephine results had a mean difference of 11% (R=0.931, P=0.0003). Bone marrow trephine and bone marrow aspiration results had a mean difference of 7% (R=0.957, P=0.005). Summary/Conclusion: In conclusion there was no major discrepancies between the results of immunophenotyping with flow cytometry, bone marrow aspiration and bone marrow trephine. Hence, there is no concern in the current medical practice for detecting AML patient’s myeloblast percentage, and therefore no intervention is required. Keywords: Bone marrow biopsy, Acute myeloid leukemia, Flow cytometry
PB1848: IN VITRO CHEMOSENSITIVITY ASSAY PREDICTS TREATMENT RESPONSE IN RELAPSED AND REFRACTORY ACUTE MYELOID LEUKEMIA
Authors: Yigeng Cao, LI Liu, Erlie Jiang
Journal: HemaSphere (2023)

Topic: 4. Acute myeloid leukemia - Clinical Background: Relapsed and refractory acute myeloid leukemia (R/R AML) carries a poor prognosis with few effective treatment options. Rapid in vitro expansion of patient-derived tumor cells and high-throughput screening for drug sensitivity can customize individualized drug regimens for cancer patients. This therapeutic landscape provides an opportunity to revisit the approach to R/R AML. Aims: To evaluate the efficacy and safety of an individualized regimen based on drug sensitivity in the treatment of R/R AML. Methods: The ongoing, prospective, single-center, exploratory study (NCT04808037) aims to enroll 50 patients with R/R AML from the Institute of Hematology & Blood Diseases Hospital. Leukemia cells from bone marrow of patients were collected, isolated and cultured for drug sensitivity screening (drug regimens included Mitoxantrone liposome, Venetoclax, Azacitidine, Selinexor, Homoharringtonine, Gilteritinib Cytarabine and Cyclophosphamide). Individualized treatment plans were formulated based on the results of drug sensitivity screening. Results: Of 11 patients included between May 2022 and January 2023, the median age was 39 years (range 22–60), 6(54.55%) patients were relapsed after hematopoietic stem-cell transplantation (HSCT) and 5(45.45%) were relapsed during chemotherapy, and 2 were refractory AML (who failed at least two prior therapy). 11 patients were evaluable for efficacy. At a median follow up of 1.54 months (range 0.72–5.98), the consistency rate between the results of highthrough put drug sensitivity screen in vitro and the clinical efficacy was 54.55%(6/11). 7 patients achieved the composite complete response (CRc) and the overall response (ORR) rate and the CRc rate were both 63.64%. The ORR rate of patients relapsed after HSCT was even higher than that of patients who were refractory or relapsed during chemotherapy (66.67% vs 60%). In the single drug sensitivity test, mitoxantrone hydrochloride liposome injection was a highly sensitive drug, and most of the patients were treated with combination regimens consisted of mitoxantrone hydrochloride liposome. According to CTCAE 5.0 grading, hematological adverse effects were the most common (79%, n=9), including neutropenia (64%, n=7), and thrombocytopenia (81.82%, n=9). No death has been attributed to the therapy. Summary/Conclusion: In R/R AML patients, individualized regimen based on drug sensitivity assay shows high efficacy and safety, especially in the combination regimens containing mitoxantrone liposome.Keywords: Acute myeloid leukemia, relapsed/refractory
PB2444: IMPACT OF LYMPHOCYTOSIS ON LONG-TERM CLINICAL OUTCOMES AFTER ALLOGENIC STEM CELL TRANSPLANTATION
Authors: Dorra Belloumi, Insaf Ben Yaiche, Fatma Essid, Ouerghi Rihab, Nour Ben Adejlil, Lamia Torjemane, Ines Turki, Sabrine Mekni, Saloua Ladeb, Tarek Ben Othman
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Sustained lymphocytosis can occur as a result of constant antigenic stimulation in various situations such as allogenic stem cell transplantation (allo-SCT) and chronic CMV or VZV infections. Aims: Our aim was to assess the impact of lymphocytosis on transplant-related outcomes. Methods: We retrospectively examined the occurrence of sustained lymphocytosis after allo-SCT, performed in our center, between January 2012 and December 2016 for hematological malignancies. Patients that had survived beyond day 100 were included. Lymphocytosis was defined as a sustained elevation in the absolute lymphocyte count above 4 x 109/L, observed in at least 3 consecutive determinations over a time frame of 3 months. Results: Our study was conducted on 138 consecutive patients. The median age was 32 years (5-56) with a sex ratio of 1.5. The main underlying diseases were acute myeloblastic leukemia (n=62), acute lymphoblastic leukemia (n=48) and lymphoma (n=15). After a median follow-up of 5 years (3 months-11 years), 23 patients (16.6%) developed lymphocytosis during their post-transplant course. The median onset of lymphocytosis was of 9 months (1 month- 5 years) with a median duration of 3 years (9 months-7 years) and a median lymphocyte count of 5.1x109/L (4.1-10.3). The cumulative incidence of lymphocytosis at 1, 2 and 5 years was 10.3%, 12.5% and 13%. Patients with lymphocytosis showed an OS advantage at 5 years (78.3% vs 53.5%, p=0.02). Although not statistically significant, there was a trend towards lower non-relapse mortality (18.6% vs 31%, p=0.075) and lower relapse incidence (26.6% vs 42%, p=0.2). Factors classically associated with the development of lymphocytosis were studied but our results were not statistically significant: chronic GVHD (56% vs 43%, p=0.26), CMV reactivation (43% vs 35%, p=0.48). Conclusion: In our cohort, post-allo-SCT lymphocytosis seems to be associated with favorable outcomes, in accordance with many published reports. A better characterization of this lymphocytosis is necessary by morphological and immunophenotypical study. Keywords: Allogeneic hematopoietic stem cell transplant, Graft-versus-host disease (GVHD), CMV infection, Absolute lymphocyte count
P1591: IMPACT OF COVID-19 ON THE EVOLUTION OF PRE-EXISTING PRIMARY IMMUNE THROMBOCYTOPENIA: A PROSPECTIVE OBSERVATIONAL STUDY
Authors: Haixia Fu, Zhuo-Yu An, Qiu-Sha Huang, Ye-Jun Wu, Feitong Meng, Song Wang, Chengjie Feng, Keting Tong, Yue Jing, Yimeng LI, Xueqi LI, Menglin LI, Mengyu Xiao, Yuxiu Chen, Chen Zhao, Jianying Zhou, Xiao-Hui Zhang, Xiao-Jun Huang
Journal: HemaSphere (2023)
P643: CUMULATIVE REVIEW OF HEART FAILURE WITH ACALABRUTINIB IN THE TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA USING DATA FROM CLINICAL TRIALS AND POST-MARKETING EXPERIENCE
Authors: Paolo Ghia, Manan Pareek, Shogheeg Apkarian Bourjlian, Naghmana Bajwa, Anthony J. Corry, Suman Jannuru, Georg Kreuzbauer, Husam Abdel-Qadir
Journal: HemaSphere (2023)

Background: Bruton tyrosine kinase inhibitors (BTKis) have revolutionized treatment for several B-cell malignancies. However, the first-generation BTKi ibrutinib has been linked with cardiac toxicities including atrial fibrillation, ventricular tachyarrhythmias, hypertension, and heart failure (HF). The predominantly elderly population with chronic lymphocytic leukemia (CLL) is expected to be at increased risk of cardiovascular disease, including HF. Aims: To review the acalabrutinib safety profile with respect to HF based on phase 3 randomized clinical trial data and the global acalabrutinib safety database. Methods: Safety data were obtained from 3 phase 3 CLL trials (ELEVATE-RR, ELEVATE-TN, ASCEND) and from the global acalabrutinib safety database, which includes all clinical trial and post-marketing data for acalabrutinib. In the individual phase 3 clinical trials for the acalabrutinib and active comparator arms, exposure-adjusted (exp-adj) incidence rates (events/100 person-months) were reported for “cardiac failure” (CF) using the broad Standardized MedDRA Query (SMQ; comprising CF-specific and CF-related terms) and the MedDRA preferred terms (PT). Exp-adj incidence rates of CF also were reported based on a cumulative comprehensive search of the global acalabrutinib safety database. Results: In the 3 clinical trials, 598 patients were treated with acalabrutinib monotherapy, 178 with acalabrutinib + obinutuzumab, and 586 with comparator anti-neoplastic agents. In each of the 3 clinical trials, the overall exp-adj incidence rates of any-grade and grade ≥3 CF (SMQ) were numerically lower in the acalabrutinib arms vs comparator arms; the most common PTs were generally numerically lower in the acalabrutinib arms (Table). The exp-adj incidence rate of any-grade CF (PT) in the acalabrutinib arms across the 3 trials ranged from 0.03 to 0.06 (Table); the corresponding exp-adj incidence rate of any-grade CF from the global acalabrutinib safety database (post-marketing sources only) was 0.008. In the global acalabrutinib safety database, a total of 779 CF (SMQ) events were captured (727 from post-marketing sources), of which the most commonly reported CF terms were peripheral swelling (n=406), edema peripheral (n=99), edema (n=56), and pulmonary edema (n=47). Summary/Conclusion: Cumulatively, overall exp-adj incidence estimates for CF events from 3 clinical trials in CLL were not higher with acalabrutinib monotherapy than with other antineoplastic agents, irrespective of severity. Data from the clinical trial and global safety databases do not suggest that acalabrutinib is associated with a substantially higher risk of CF.Keywords: Clinical trial, Chronic lymphocytic leukemia, Safety